Chronic Reproductive Toxicity Thresholds for Northern Bobwhite Quail (Colinus virginianus) Exposed to Perfluorohexanoic Acid (PFHxA) and a Mixture of Perfluorooctane Sulfonic Acid (PFOS) and PFHxA

Abstract

Terrestrial toxicology data are limited for comprehensive ecotoxicological risk assessment of ecosystems contaminated by per‐ and polyfluoroalkyl substances (PFAS) partly because of their existence as mixtures in the environment. This complicates logistical dose–response modeling and establishment of a threshold value characterizing the chronic toxicity of PFAS to ecological receptors. We examined reproduction, growth, and survival endpoints using a combination of hypothesis testing and logistical dose–response modeling of northern bobwhite quail (Colinus virginianus) exposed to perfluorohexanoic acid (PFHxA) alone and to PFHxA in a binary mixture with perfluorooctane sulfonic acid (PFOS) via the drinking water. The exposure concentration chronic toxicity value (CTV) representative of the lowest‐observable–adverse effect level (LOAEL) threshold for chronic oral PFAS toxicity (based on reduced offspring weight and growth rate) was 0.10 ng/mL for PFHxA and 0.06 ng/mL for a PFOS:PFHxA (2.7:1) mixture. These estimates corresponded to an adult LOAEL average daily intake CTV of 0.0149 and 0.0082 µg × kg body weight–1 × d–1, respectively. Neither no‐observable–adverse effect level threshold and representative CTVs nor dose–response and predicted effective concentration values could be established for these 2 response variables. The findings indicate that a reaction(s) occurs among the individual PFAS components present in the mixture to alter the potential toxicity, demonstrating that mixture affects avian PFAS toxicity. Thus, chronic oral PFAS toxicity to avian receptors represented as the sum of the individual compound toxicities may not necessarily be the best method for assessing chronic mixture exposure risk at PFAS‐contaminated sites. Environ Toxicol Chem 2021;40:2601–2614. © 2021 SETAC

Species‐ and Tissue‐Specific Chronic Toxicity Values for Northern Bobwhite Quail (Colinus virginianus) Exposed to Perfluorohexane Sulfonic Acid and a Binary Mixture of Perfluorooctane Sulfonic Acid and Perfluorohexane Sulfonic Acid

“…Collectively, these outcomes demonstrate that PFOS accumulates differently in female versus male northern bobwhite quail liver tissues when mixed with either PFHxS or PFHxA, and indicate that PFOS accumulation due to chronic oral exposure partially depends on the presence of other PFAS (Dennis, Subbiah, et al, 2021; present study). These observations indicate that PFAS mixtures play an important role in chronic avian PFAS toxicity (Dennis et al, 2020; Dennis, Hossain, et al, 2021; Dennis, Subbiah, et al, 2021). As a result, we caution that PFAS ERAs completed prior to these pivotal studies may underestimate potential health risk to avian or other terrestrial receptors (Conder et al, 2020; Divine et al, 2020; Gobas et al, 2020; Larson et al, 2018; Zodrow et al, 2021), and we encourage adoption of these new PFAS LOAEL CTVs in future PFAS ERAs.…”

“…This range brackets residues (corresponding to chronic oral toxicity) quantified from the liver of adult and/or juvenile northern bobwhite quail specimens (less than detection limit–133.8 ng/g wet wt; see: Dennis, Subbiah, et al, 2021, repository data) exposed to PFOS and PFHxS at concentrations and mixture ratios typically found in the environment (Anderson et al, 2016; Dennis et al, 2020; East et al, 2020; Filipovic et al, 2015). The present study examined and reported the residues from the livers of adult and juvenile northern bobwhite quail specimens chronically exposed to either PFHxA alone or a binary mixture containing PFOS (Dennis, Hossain, et al, 2021) for a better understanding of the chronic oral toxicity of PFAS to avian receptors.…”

“…These observations align with our current understanding of the bioaccumulation potential of shorter versus longer chain PFAS but are contrary to our current knowledge regarding the toxic potential of sulfonated versus carboxylated PFAS (see Ankley et al, 2021; Holmström & Berger, 2008; McCarthy et al, 2017; Verreault et al, 2005; Zodrow et al, 2021). A comparison between studies demonstrates that PFHxA in drinking water (a shorter chained, carboxylated PFAS) may be toxic to northern bobwhite quail whether administered alone or in a binary mixture with PFOS (a longer chained, sulfonated PFAS) at much lower exposure concentrations than PFOS administered alone or in a binary mixture with PFHxS (a shorter chained, sulfonated PFAS; Dennis et al, 2020; Dennis, Hossain, et al, 2021). However, lacking a comparable avian PFHxA dietary exposure study, this observation cannot be confirmed.…”

“…The test chemicals used were previously characterized and verified for branching and purity (Dennis, Hossain, et al, 2021). Closely following the Dennis, Subbiah, et al (2021) study methods coupled with PFAS analytical guidance (USEPA, 2009, 2016), the recoveries were quantified for each test chemical (i.e., neat undecafluorohexanoic acid [PFHxA] liquid from Wellington Laboratories and heptadecafluorooctanesulfonic acid [PFOS] potassium salt from Sigma‐Aldrich) and the surrogate standard (N‐methyl‐d 3 ‐perfluoro‐1‐octanesulfonamidoacetic acid [d 3 ‐N‐MeFOSAA]; Wellington Laboratories).…”

“…Presuming that PFOS is the most toxic individual PFAS, and assuming additive toxicity, a comparison of ∑PFAS measured or modeled with the avian PFOS TRV would be a conservative approach for PFAS risk assessment. However, studies have shown that interactions occur among individual PFAS in mixtures, causing differences in toxicity to model organisms (Bursian et al, 2020; Dennis et al, 2020; Dennis, Hossain, et al, 2021; Dennis, Subbiah, et al, 2021; Flynn et al, 2019). Universally assuming additivity of PFAS toxicity to terrestrial ecological receptors may be incorrect, and could lead to underestimates of risk.…”